As of 2015, 46.8 million individuals worldwide are estimated to have dementia, and it is thought to double every 20 years, eventually reaching 74.7 million in 2030 and 131.5 million in 2050. Dementia is defined as a mental disorder caused by brain disease or injury to the brain, which can result in memory disorders, personality changes, and impaired reasoning. In the United States, Alzheimer’s disease (AD) has been reported as the 6th leading cause of death, but is the 5th leading cause of death for individuals who are 65+ years of age and is responsible for 60-80% of cases pertaining to patients with dementia. New estimates by the World Alzheimer’s Report of 2015 have shown a 12-13% increase of individuals diagnosed with AD when compared to the estimates made by the same report in 2009, meaning that individuals are being diagnosed with AD at greater rates than predicted in 2009. An estimated $200 billion have been reported for the treatment of patients with AD in 2012. Memantine hydrochloride (HCl), an N-methyl-D-aspartate receptor antagonist (NMDA), and donepezil HCl, an acetylcholinesterase inhibitor, are oral pharmaceuticals used to treat Alzheimer’s disease. The price of Namenda® (memantine HCl) is reported to be an average of $382.13 for 30 capsules, and an average of $163.64 for 30 capsules of Aricept® (donepezil). Docking can be defined as a computational simulation used to observe whether a ligand can bind to a receptor site and how well a ligand can bind based on different conformations. By using Autodock tools and Vina (docking software), memantine and donepezil were docked onto an NMDA receptor for the purpose of understanding which ligand has a greater affinity to the NMDA receptor by systematically evaluating their active conformations, affinities, and location of binding. When comparing the highest affinities generated between donepezil and memantine HCl when docked onto the NMDA receptor, donepezil (-9.0 kCal/mol) had a higher affinity to the NMDA receptor than memantine (-6.4 kCal/mol). From this data, we can state that the oral pharmaceutical (memantine HCl) made to bind onto this protein’s receptor does not have a greater affinity than the one that was not made for this purpose (donepezil).
Victor Martinez, ’18